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Correlations between stress-associated anxiety and physiological determinants of health in adolescents

Viljoen, Monet (2016-03)

Thesis (PhD)--Stellenbosch University, 2016.

Thesis

ENGLISH ABSTRACT: Anxiety disorders are among the most prevalent of psychiatric disorders across age groups, with onset typically in childhood or early adolescence, and risk for developing an anxiety disorder increasing with trauma/childhood maltreatment. Little is known about biomarkers of resilience/vulnerability in relation to subclinical anxiety, especially when trauma-exposed adolescents are implicated. Therefore, better elucidation of the neuro-endocrine and -immunological underpinnings relative to anxiety and trauma, may highlight specific avenues to target with more effective diagnosis, monitoring and/or treatment strategies in the context of youth at risk for later development of anxiety disorders. Thus, our aims were to elucidate the central and peripheral neuroendocrine and immunological profiles in association with anxiety proneness, in comparison to childhood trauma, in older adolescents, and to assess potential outcome modulators.
A total of 43 participants, aged 15-18, were selected from an initial cohort of 1149 adolescents. Participants were delineated into four groups based on levels of anxiety proneness and trauma exposure, using questionnaires and a structured diagnostic interview. Blood obtained from each participant was analysed for an HPA-axis hormone profile (cortisol, prolactin, testosterone and dehydroepiandrosterone-sulphate (DHEAs) and immune status (total white blood cell count, leukocyte glucocorticoid receptor (GR) expression and serum cytokine and myeloperoxidase (MPO) levels). Resilience (coping capacity), self-esteem and handedness were assessed via questionnaires. Verbal- and visuospatial working memory, as well as executive neurocognitive function, were assessed by means of the administration of neurocognitive tests. A structural Magnetic Resonance Imaging (MRI) was performed to determine left versus right grey matter volumes of the thalamus, amygdala, hippocampus, and Prefrontal cortex (PFC). Finally, HPA-axis responsivity and concurrent state anxiety to an in vivo Bexamethasone suppression test, in conjunction with as a psychosocial stress test (TSST), were assessed.
In terms of neurophysiological maladaptations, main findings included a relatively larger association with anxiety proneness, compared to childhood maltreatment. Specifically, anxiety proneness was associated with poorer neurocognitive function, increased right amygdala volume, lower serum DHEAs levels, lower peripheral leukocyte counts, and increased GR expression. In terms of potential outcome modifying factors (OMFs), resilience and self-esteem were affected by trauma, but not anxiety proneness, while a higher degree of right handedness was associated with poorer neurophysiological outcomes. Furthermore, increased serum IL-12p70 and MPO (suggesting relatively more pro-inflammatory state) were associated with anxiety scales and emotional/physical abuse. Also, better PFC neurocognitive function and larger left PFC volumes were associated with better physiological outcome as indicated by levels of GR expression and DHEAs.
In conclusion, this is the first study to have investigated neurophysiological adaptations, as well as psycho-physiological responses to HPA-axis suppression and a psychosocial stress test, in association with anxiety proneness and trauma exposure, in adolescents of low socio-demographic background. Results suggest for the study population, a) chronic hypo-activity and acute hypo-reactivity of the lower HPA-axis, b) neurophysiological perturbations associated relatively closely with anxiety proneness, when compared to trauma exposure, c) central correlates associated with physiological outcome, and d) a higher degree of consistent right handedness to be a potential marker of vulnerability in terms of neurophysiology and anxiety.